Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells

Abstract Differentiation therapy is attracting increasing interest in cancer as it can be more specific than conventional chemotherapy approaches, and it has offered new treatment options for some cancer types, such as treating acute promyelocytic leukaemia (APL) by retinoic acid. However, there is...

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Autores principales:	Yasaman KalantarMotamedi, Fatemeh Ejeian, Faezeh Sabouhi, Leila Bahmani, Alireza Shoaraye Nejati, Aditya Mukund Bhagwat, Ali Mohammad Ahadi, Azita Parvaneh Tafreshi, Mohammad Hossein Nasr-Esfahani, Andreas Bender
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/02ed4f38dc9a40a2941f06dfeba4ddb2
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spelling	oai:doaj.org-article:02ed4f38dc9a40a2941f06dfeba4ddb22021-12-02T16:04:19ZTranscriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells10.1038/s41598-021-91629-x2045-2322https://doaj.org/article/02ed4f38dc9a40a2941f06dfeba4ddb22021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91629-xhttps://doaj.org/toc/2045-2322Abstract Differentiation therapy is attracting increasing interest in cancer as it can be more specific than conventional chemotherapy approaches, and it has offered new treatment options for some cancer types, such as treating acute promyelocytic leukaemia (APL) by retinoic acid. However, there is a pressing need to identify additional molecules which act in this way, both in leukaemia and other cancer types. In this work, we hence developed a novel transcriptional drug repositioning approach, based on both bioinformatics and cheminformatics components, that enables selecting such compounds in a more informed manner. We have validated the approach for leukaemia cells, and retrospectively retinoic acid was successfully identified using our method. Prospectively, the anti-parasitic compound fenbendazole was tested in leukaemia cells, and we were able to show that it can induce the differentiation of leukaemia cells to granulocytes in low concentrations of 0.1 μM and within as short a time period as 3 days. This work hence provides a systematic and validated approach for identifying small molecules for differentiation therapy in cancer.Yasaman KalantarMotamediFatemeh EjeianFaezeh SabouhiLeila BahmaniAlireza Shoaraye NejatiAditya Mukund BhagwatAli Mohammad AhadiAzita Parvaneh TafreshiMohammad Hossein Nasr-EsfahaniAndreas BenderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yasaman KalantarMotamedi Fatemeh Ejeian Faezeh Sabouhi Leila Bahmani Alireza Shoaraye Nejati Aditya Mukund Bhagwat Ali Mohammad Ahadi Azita Parvaneh Tafreshi Mohammad Hossein Nasr-Esfahani Andreas Bender Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells
description	Abstract Differentiation therapy is attracting increasing interest in cancer as it can be more specific than conventional chemotherapy approaches, and it has offered new treatment options for some cancer types, such as treating acute promyelocytic leukaemia (APL) by retinoic acid. However, there is a pressing need to identify additional molecules which act in this way, both in leukaemia and other cancer types. In this work, we hence developed a novel transcriptional drug repositioning approach, based on both bioinformatics and cheminformatics components, that enables selecting such compounds in a more informed manner. We have validated the approach for leukaemia cells, and retrospectively retinoic acid was successfully identified using our method. Prospectively, the anti-parasitic compound fenbendazole was tested in leukaemia cells, and we were able to show that it can induce the differentiation of leukaemia cells to granulocytes in low concentrations of 0.1 μM and within as short a time period as 3 days. This work hence provides a systematic and validated approach for identifying small molecules for differentiation therapy in cancer.
format	article
author	Yasaman KalantarMotamedi Fatemeh Ejeian Faezeh Sabouhi Leila Bahmani Alireza Shoaraye Nejati Aditya Mukund Bhagwat Ali Mohammad Ahadi Azita Parvaneh Tafreshi Mohammad Hossein Nasr-Esfahani Andreas Bender
author_facet	Yasaman KalantarMotamedi Fatemeh Ejeian Faezeh Sabouhi Leila Bahmani Alireza Shoaraye Nejati Aditya Mukund Bhagwat Ali Mohammad Ahadi Azita Parvaneh Tafreshi Mohammad Hossein Nasr-Esfahani Andreas Bender
author_sort	Yasaman KalantarMotamedi
title	Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells
title_short	Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells
title_full	Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells
title_fullStr	Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells
title_full_unstemmed	Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells
title_sort	transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/02ed4f38dc9a40a2941f06dfeba4ddb2
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Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells

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